Weixing Deng

Monodispersed Brush-Like Conjugated Polyelectrolyte Nanoparticles with Efficient and Visualized SiRNA Delivery for Gene Silencing

RNA interference is supposed to be one of the most powerful technologies for suppression of genes and treatment of diverse human diseases while the safe delivery and visualization of siRNA were still challenging. In this text, a novel type of monodispersed conjugated polymer nanoparticles PFNBr with brush-like molecular structure was introduced into siRNA delivery system. The nanoparticles exhibited dual functions conveniently in the delivery system which can not only carry high amount of siRNA to penetrate intracellularly for knocking down targeted mRNA but also act as signal agents for siRNA tracking and cellular imaging. Due to the high density side chains with positive charges and more extended conformation of the spatial structure, PFNBr nanoparticles as nanocarrier for siRNA provided outstanding capture ability (1 mol polymer to more than 32.5 mol siRNA) and enhanced protection capability of siRNA molecules from degradation. Here, it should be noted that the concentration of carrier in the working platform was lowered from the level of μmol/L to nmol/L compared with other conjugated polymer delivery systems due to the outstanding carrying capacity of PFNBr. And meanwhile, this system acquired high gene silence efficiency and good biocompatibility. The proposed complex nanoparticles efficiently transfected siPlk1 into PANC-1 cells and induced high knockdown efficiency for targeted Plk1 mRNA to 23.9% and no significant cytotoxicity of the PFNBr/siRNA complexes was shown. Therefore, this working platform provides a solution to most of the common problems associated with the siRNA delivery, visualization, and therapeutic applications, and keeps a bright outlook for the development of new nucleic acid-based therapeutics and simultaneously for fluorescent bioimaging.

Monodispersed grafted conjugated polyelectrolyte-stabilized magnetic nanoparticles as multifunctional platform for cellular imaging and drug delivery

An anionic grafted conjugated polyelectrolyte was synthesized, and then magnetic nanoparticles stabilized with this material were successfully prepared by a convenient method and used for bioimaging and drug delivery. Grafted conjugated polymer (PFPAA) containing abundant carboxyl groups was attached to the surface of Fe3O4 nanoparticles through ligand exchange with oleic acid and anionic grafted conjugated polyelectrolyte-stabilized magnetic nanoparticles (MNPs@PFPANa) were then obtained by ionization with sodium carbonate. These as-synthesized nanoparticles showed good water solubility and stability, with no precipitation observed in 8 months, and had a narrow size distribution with a mean hydrodynamic diameter of 26 ± 2.4 nm. In addition, these nanoparticles exhibited superparamagnetic properties with a saturation magnetization (Ms) of 20 emu g-1, which sufficient for bioapplications. Upon 48 h incubation with macrophage cells, the obtained nanoparticles showed good biocompatibility of 2 pg Fe per cell as measured by ICP-OES. Furthermore, MNPs@PFPANa were low toxicity as confirmed by an MTT assay using NIH-3T3 fibroblasts. Confocal microscopy results revealed that MNPs@PFPANa can be retained in cytoplasm with high fluorescence. MNPs@PFPANa exhibited good DOX drug loading efficiency of about 10 wt% and showed good therapeutic efficiency for BGC-823 cancer cells. These results indicated such multifunctional nanoparticles would be useful in bioimaging and as drug carriers for cancer treatment.

High Density Glycopolymers Functionalized Perylene Diimide Nanoparticles for Tumor-Targeted Photoacoustic Imaging and Enhanced Photothermal Therapy

Near-infrared (NIR) absorbing nanoagents with functions of photoacoustic imaging (PAI) and photothermal therapy (PTT) have received great attention for cancer therapy. However, endowing them with multifunctions, especially targeting ability, for enhancing in vivo PAI/PTT generally suffers from the problems of synthetic complexity and low surface density of function groups. We herein report high density glycopolymers coated perylenediimide nanoparticles (PLAC-PDI NPs), self-assembled by poly(lactose)-modified perylenediimide (PLAC-PDI), as tumor-targeted PAI/PTT nanoagents. Atom transfer radical polymerization and click reaction were used in sequence to prepare PLAC-PDI, which can accurately control the content of poly(lactose) (PLAC) in PLAC-PDI and endow PLAC-PDI NPs with high density PLAC surface. The high density PLAC surface provided NPs with long-time colloidal stability, outstanding stability in serum and light, and specific targeting ability to cancer cells and tumors. Meanwhile, PLAC-PDI NPs also presented high photothermal conversion efficiency of 42% by virtue of strong π-π interactions among perylenediimide molecules. In living mice, PAI experiments revealed that PLAC-PDI NPs exhibited effective targeting ability and enhanced PTT efficacy to HepG2 tumor compared with control groups, lactose blocking, and ASGP-R negative tumor groups. Overall, our work provids new insights for designing glycopolymers-based therapeutic nanoagents for efficient tumor imaging and antitumor therapy.

Zwitterionic diketopyrrolopyrrole for fluorescence/photoacoustic imaging guided photodynamic/photothermal therapy

Dual-modal imaging and dual-modal therapy provide multiple complementary theranostic features. The theranostic agent has favorable renal excretion and low cytotoxicity, making it of great interest in the nanomedical field. Herein, a water-soluble conjugated zwitterionic polymer (DPP-SPMA) with low-fouling and low cytotoxicity was prepared and used for fluorescence/PA imaging guided PTT/PDT therapy. The in vivo imaging results showed that the DPP-SPMA had excellent enhanced permeability and retention effects. The fluorescence imaging demonstrated that the DPP-SPMA was excreted by renal metabolism because the controlled molecular mass was less than the renal filtration threshold. The DPP-SPMA shows a photothermal effect under 730 nm irradiation and an excellent singlet oxygen generation capacity for the PDT therapy under 635 nm irradiation. The high accumulation of DPP-SPMA by passive targeting around the tumor stimulated excellent synergistic photodynamic therapy and photothermal therapy. As a result, the water-soluble zwitterion DPP-SPMA was well suited for fluorescence/PA dual-modal imaging and had significant antitumor activity in vivo via synergistic photodynamic therapy and photothermal therapy.

A water-soluble phosphorescent conjugated polymer brush for tumor-targeted photodynamic therapy

Photodynamic therapy (PDT) has become a promising treatment approach against cancer due to low side effects and high therapeutic efficacy. However, the limitations of photosensitizers such as poor water solubility and lack of targeting ability hindered the clinical application of PDT. Here, we synthesized a phosphorescent conjugated polymer brush (PPF-Ir-g-(POEGMA-b-PGal)) in which a small photosensitizer iridium(III) complex was covalently attached to the conjugated backbone. A further hydrophilic polymer (POEGMA) and glycopolymer polygalactose (PGal), which has a specific binding ability with Hep G2 tumors, were grafted from the conjugated backbone via atom transfer radical polymerization (ATRP) and click reaction. The brush structure rendered PPF-Ir-g-(POEGMA-b-PGal) exhibited excellent water solubility. Meanwhile, PPF-Ir-g-(POEGMA-b-PGal) showed efficient properties of producing singlet oxygen. The photodynamic effect of the PPF-Ir-g-(POEGMA-b-PGal) photosensitizer was evaluated in Hep G2 cells via the MTT assay and flow cytometry and the results indicated that this photosensitizer can efficiently cause the death of cancer cells. Additionally, an antitumor study of PPF-Ir-g-(POEGMA-b-PGal) was conducted in vivo with Hep G2 tumor bearing nude mice, and the results show that the xenograft tumors were significantly inhibited. In summary, PPF-Ir-g-(POEGMA-b-PGal) exhibited fine water solubility and high PDT efficiency both in vitro and in vivo. Our study may further encourage the applications of conjugated polymer brush based photosensitizers for PDT in tumor treatment.

A macrocyclic oligoelectrolyte as a facial platform for absorbing hyaluronic acid oligomers for targeted cancer cellular imaging

A novel water-soluble macrocyclic oligoelectrolyte (MOE) was designed and synthesized by a simple Friedel–Crafts reaction as a facial platform for fabricating biological nanoparticles. The produced MOE with a unique three-dimension (3D) rigid structure consisted of a triphenylamine-based cyclic core and three oligofluorene arms, which protruded from the ring plane on both sides. The specific structure rendered MOE with good photoluminescence (PL) stabilities, low aggregation tendencies and excellent water-soluble properties in the form of well-defined smart organic dots (sub-10 nm) in aqueous solution. Using these organic dots as a template and OHAs, a biocompatible and linear oligosaccharide made straightforward contact with CD44 (a principal cell surface receptor for HA). As a stabilizer and biomarker, functional nanoparticles (MHNs-0.4) were fabricated via electronic interaction induced self-assembly in aqueous solution. The final confirmed MHNs-0.4 with suitable size (around 80 nm), good stability and fluorescent properties were found to be outstanding materials for the specific labelling of CD44-overexpressed human lung cancer cells (A549). The highlight of the study is that we provided a powerful and reliable platform, MOE-dots, for adsorbing various negatively charged molecules and broadening potential biological applications.

A perylene diimide zwitterionic polymer for photoacoustic imaging guided photothermal/photodynamic synergistic therapy with single near-infrared irradiation

Phototherapy has great promise for precise cancer diagnosis and effective therapy, but the development of one multifunctional nanoplatform for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) at a single excitation wavelength remains a challenge. In this work, a perylene diimide zwitterionic polymer PDS-PDI was synthesized via atom transfer radical polymerization (ATRP). This polymer was designed for photoacoustic imaging (PAI) guided synergistic PDT and PTT with single 660 nm near-infrared (NIR) light irradiation. The prepared PDS-PDI polymer presents high photothermal conversion efficiency (η≈ 40%) and efficient singlet oxygen quantum yield (ΦΔ≈ 16.7%) under 660 nm laser irradiation. Polymer PDS-PDI also acts as a contrast agent for PAI, offering real-time monitoring in tumor sites. Additionally, in vitro and in vivo assays indicate that polymer PDS-PDI has good biocompatibility and effective tumor destruction ability under 660 nm laser irradiation. In brief, polymer PDS-PDI prepared in this study could be applied as a dual-mode phototherapeutic agent under single laser irradiation.